Biomira initiates Phase 1 trial of PX-478 in patients with advanced metastatic cancers
"HIF-1 alpha plays a critical role in the response of cancer cells to lowoxygen levels, stimulating processes that increase oxygen concentrations andallow tumors to grow and thrive," said Dr. Lynn Kirkpatrick, Ph.D., ChiefScientific Officer of Biomira. "In our preclinical studies, PX-478 producedsignificant tumor regression and growth delay in a wide variety of models ofhuman cancers, including lung, breast, prostate, colon, kidney, pancreas, andovarian cancers. We believe this is the first small molecule agent to enterclinical trials that directly lowers levels of HIF-1 alpha protein in tumors."
The Phase 1 trial is expected to enroll up to 36 patients with advancedsolid tumors or lymphoma who have failed or are intolerant of standardtherapy. PX-478 will be administered orally on days 1 through 5 of a 21-daycycle. Primary objectives of the study include establishment of a maximumtolerated dose, evaluation of safety, and analyses of pharmacodynamic andpharmacokinetic profiles of PX-478. Other objectives are to evaluate theeffects of PX-478 on tumor blood flow and vascular permeability as measured byDCE-MRI, and to evaluate the anti-tumor activity of PX-478 in patients withadvanced malignancies.
"We are very excited about the potential for PX-478 as an anti-cancercompound with broad potential application," said Dr. Robert L. Kirkman, MD,President and Chief Executive Officer of Biomira. "We are also pleased withthe progress of our pipeline, as demonstrated by the initiation of this trialon schedule. This is our second small molecule compound to enter clinicaldevelopment, and we expect to file an investigational new drug (IND)application for PX-866, a third small molecule, by the end of 2007. Togetherwith PX-12, currently in Phase 2 development, the advancement of thesecompounds reflects our significant progress in creating value from ouracquisition of ProlX Pharmaceuticals less than one year ago."
PX-478 is a potent inhibitor of HIF-1 alpha, a protein target whose levelsare elevated in a wide range of tumors. The protein is a key factor in theresponse of a cancer cell to hypoxia (lack of oxygen), including theangiogenic cascade that allows tumors to establish new blood vessels essentialto their survival and growth. Inhibition of angiogenesis is a validatedapproach to treating cancer.
In preclinical studies, PX-478 demonstrated marked antitumor activity whendelivered orally, showing tumor regression and long growth delay, both ofwhich correlated to the HIF-1 alpha levels of the tumor models. The widevariety of models that showed sensitivity to PX-478 presents a large potentialmarket for this product candidate. The ability to combine PX-478 withradiation therapy may further expand the opportunities for this novelcompound. The PX-478 preclinical development work was partially supported by agrant from the U.S National Institutes of Health Small Business InnovationResearch program.
Biomira is a biotechnology company specializing in the development ofinnovative therapeutic products for the treatment of cancer. Biomira's goal isto develop and commercialize novel synthetic vaccines and targeted smallmolecules that have the potential to improve t
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